Improved methods and compositions for F-18 labeling of proteins, peptides and other molecules

Abstract

The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules (including but not limited to aptamers, oligonucleotides and nucleic acids) may be labeled and utilized for such imaging studies. In preferred embodiments, the F-18 label may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety (such as DOTA, NOTA, DTPA, TETA or NETA). In other embodiments, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other preferred embodiments, the F-18 labeled moiety may comprise a targetable conjugate that may be used in combination with a bispecific or multispecific antibody to target the F-18 to an antigen expressed on a cell or tissue associated with a disease, medical condition, or pathogen. Exemplary results show that F-18 labeled targetable conjugate peptides are stable in human serum at 37 DEG C for several hours, sufficient time to perform PET imaging analysis.

Description

[0001] related application [0002] This application is a continuation-in-part of U.S. Patent Application No. 11 / 960,262, filed December 19, 2007, which requires U.S. Provisional Patent Application No. 60, filed January 11, 2007, under U.S.C. § 119(e) / 884,521, both of which are incorporated by reference in their entirety. technical field [0003] In certain embodiments, the present invention relates to a simple method of labeling peptides with F-18, which can be used for in vivo imaging. The preferred specific activity of the F-18 labeled peptide is about 1,000 to 2,000 Ci / mol when administered to a subject. Specific activities in the range of 100 to tens of thousands of Ci / mmol can also be used. While higher specific activity is preferred in certain imaging applications, in other alternatives lower specific activity NOTA (1,4,7-triaza-cyclononane-N,N',N "-triacetic acid) or another chelating moiety with a metal-F-18 complex, for example, a renal blood flow imaging agent o...

AI Technical Summary

Problems solved by technology

However, the half-life of F-18 is only 2 hours, so all the manipulations required to attach F-18 to a peptide is a significant burden

[0007] These methods are time-consuming and require the use of specially designed equipment to generate labeled products and / or the efforts of specialized chemists

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